Diabetic neuropathy is one of the most common complications of diabetes. This complication is peripheral neuropathy with predominant sensory impairment, and its symptoms begin with hyperesthesia and pain and gradually become hypoesthesia with the loss of nerve fibers. In some cases, lower limb amputation occurs when hypoalgesia makes it impossible to be aware of trauma or mechanical stimuli. On the other hand, up to 50% of these complications are asymptomatic and tend to delay early detection. Therefore, sensitive and reliable biomarkers for diabetic neuropathy are needed for an early diagnosis of this condition. This review focuses on systemic biomarkers that may be useful at this time. It also describes research on the relationship between target gene polymorphisms and pathological conditions. Finally, we also introduce current information on regenerative therapy, which is expected to be a therapeutic approach when the pathological condition has progressed and nerve degeneration has been completed.

Prednisolone is a frequently prescribed steroid with a bitter, unpalatable taste that can result in treatment refusal. Oral suspensions or powder dosage forms are often prescribed, particularly to pediatric patients, as they improve swallowability and ease of dose adjustment. Consequently, the bitterness of prednisolone is more apparent in these dosage forms. Few studies have investigated prednisolone’s bitterness. Thus, in this study, 50 adults evaluated the bitterness of prednisolone using the generalized Labeled Magnitude Scale (gLMS), in comparison with quinine, a standard bitter substance. Overall, prednisolone-saturated solution demonstrated the same extent (mean gLMS score: 46.8) of bitterness as 1 mM quinine solution (mean gLMS score: 40.1). Additionally, large individual differences were observed in the perception of the bitterness of prednisolone and quinine. Perceived flavors of some drugs are reportedly associated with bitter-taste receptor (TAS2Rs) polymorphisms. Therefore, we investigated the relationship between subjects’ genetic polymorphisms of TAS2R19, 38, and 46, and their sensitivity to bitterness. Although a relationship between TAS2R19 polymorphisms and the perception of quinine bitterness was observed, no significant relationship was found between the perceived bitterness of prednisolone and the investigated genes. Ultimately, the results show that despite individual differences among subjects, the cause of prednisolone’s strong bitterness is yet to be elucidated.

Children with Kawasaki disease are prescribed acetylsalicylic acid powder as an antipyretic analgesic and antiplatelet agent; however, some of it remains in the mouth, leading to a bitter or sour taste. To address this issue, an in-hospital mini-tablet formulation of acetylsalicylic acid was developed. In order to use the mini-tablets safely and effectively, dissolution tests alone are not sufficient. Therefore, an open-label crossover study on six healthy participants was conducted to evaluate comparative pharmacokinetic parameters. The pharmacokinetic parameters of salicylic acid were C_max: 4.80 ± 0.79 mg/L (powder; P), 5.03 ± 0.97 mg/L (mini-tablet; MT), AUC_0–12: 18.0 ± 3.03 mg-h/L (P), 18.9 ± 4.59 mg-h/L (MT), those of acetylsalicylic acid C_max: 0.50 ± 0.20 mg/L (P), 0.41 ± 0.24 mg/L (MT), AUC_0–12: 0.71 ± 0.27 mg-h/L (P), 0.61 ± 0.36 mg-h/L (MT), with no significant differences between the mini-tablet and powder formulations. Although pharmacokinetic results obtained from adults cannot be directly applied to children, the results of this study are important for predicting pharmacokinetics. Furthermore, a formulation that can improve medication adherence in children who have difficulty taking acetylsalicylic acid powder, thus contributing to pediatric drug therapy.

Background/Objectives: Orally disintegrating tablets (ODTs) are often used for patients with dysphagia; however, their co-administration with “thickened water” in clinical settings can delay disintegration and potentially reduce therapeutic efficacy. While wicking networks formed by superdisintegrants facilitate rapid disintegration, we hypothesized that viscous polymers in thickened water cause “pore clogging” within these networks. Although conventional macroscopic evaluations have demonstrated this delay, direct visualization of the underlying microstructural changes remains unexplored. Therefore, this study aimed to elucidate the microstructural mechanisms of disintegration delay. Methods: Simplified model ODTs containing either a wicking-type (crospovidone [CP]) or a swelling-type (sodium starch glycolate [SSG]) disintegrant were prepared. Their microstructures and disintegration behaviors were evaluated by cryogenic focused ion beam scanning electron microscopy (Cryo-FIB-SEM), three-dimensional (3D) X-ray computed tomography (CT), and disintegration tests under simulated gastric conditions (pH 1.2). Results: Cryo-FIB-SEM revealed that CP-containing tablets formed numerous channel-like pores that promoted capillary action upon contact with water, whereas SSG-containing tablets formed larger, isolated macropores. X-ray CT analysis demonstrated distinct low-density regions associated with penetration-induced structural changes in both formulations. In CP-containing tablets, these regions extended throughout the channel network, whereas in SSG-containing tablets they were largely confined to the tablet surface. Consequently, the disintegration of CP-containing tablets in simulated gastric fluid was significantly delayed compared to that of SSG-containing tablets. Conclusions: The findings are consistent with a pore-clogging mechanism in which penetration of a viscous medium interferes with the liquid transport pathways responsible for rapid tablet disintegration. Combined Cryo-FIB-SEM and X-ray CT imaging provided direct morphological evidence of disintegrant-dependent structural responses in viscous media and offers a new framework for mechanistic investigation of tablet disintegration processes.